First, do no harm: time for a systems approach to address the problem of health-care-derived pharmaceutical pollution
Authors: Kelly Thornber, Fiona Adshead, Angeliki Balayannis, Richard Brazier, Ross Brown, Sean Comber, Caroline Court, Iain Davidson, Michael Depledge, Caroline Farmer, Stuart Gibb, Richard Hixson, Claas Kirchhelle, Keith Moore, Marco Motta, Lydia Niemi, Stewart Owen, David Pencheon, Sharon Pfleger, Emma Pitchforth, Neil Powell, Wiebke Schmidt, Richard Smith, Georgina Sowman, Wendy Tyler-Batt, Helen Wilkinson, Edward CF Wilson, Lora Fleming, William Gaze, Charles Tyler
Journal: The Lancet Planetary Health (2022)

Chemical pollution is considered one of the nine planetary boundaries, and increasing evidence suggests that we are already operating outside of this, risking irreversible environmental change.1Persson L Carney Almroth BM Collins CD et al.Outside the safe operating space of the planetary boundary for novel entities.Environ Sci Technol. 2022; 56: 1510-1521Crossref PubMed Scopus (301) Google Scholar Pharmaceutical chemicals are vital components of modern health care, but their contamination of global waterways is threatening environmental and human health, contributing to biodiversity loss, driving antimicrobial resistance, and jeopardising progress towards the sustainable development goals.2Fuller R Landrigan PJ Balakrishnan K et al.Pollution and health: a progress update.Lancet Planet Health. 2022; 6: e535-e547Summary Full Text Full Text PDF PubMed Scopus (256) Google Scholar, 3Organisation for Economic Co-operation and DevelopmentPharmaceutical residues in freshwater: hazards and policy responses. OECD studies on water. OECD Publishing, Paris2019Google Scholar With the global pharmaceutical market now worth more than US$1·25 trillion4Alshemari A Breen L Quinn G Sivarajah U Can we create a Circular Pharmaceutical Supply Chain (CPSC) to reduce medicines waste?.Pharmacy. 2020; 8: 221Crossref Google Scholar and continuing to grow as populations age and suffer from more chronic, non-communicable diseases,5Burns EE Carter LJ Snape J Thomas-Oates J Boxall ABA Application of prioritization approaches to optimize environmental monitoring and testing of pharmaceuticals.J Toxicol Environ Health B Crit Rev. 2018; 21: 115-141Crossref PubMed Scopus (48) Google Scholar there is an urgent need to integrate pharmaceutical pollution into sustainable health-care strategies, alongside efforts to reduce carbon and plastic waste. The long-term detrimental impacts of some pharmaceuticals in the environment have been known for decades, and it is now widely recognised that ambitious legislative and non-legislative measures are required to address this issue.3Organisation for Economic Co-operation and DevelopmentPharmaceutical residues in freshwater: hazards and policy responses. OECD studies on water. OECD Publishing, Paris2019Google Scholar Progress to date has been restricted largely because of a focus on improving human health and financial outcomes, and the complexity of global pharmaceutical value chains.3Organisation for Economic Co-operation and DevelopmentPharmaceutical residues in freshwater: hazards and policy responses. OECD studies on water. OECD Publishing, Paris2019Google Scholar High-income countries (HICs) are the major consumers of pharmaceuticals,3Organisation for Economic Co-operation and DevelopmentPharmaceutical residues in freshwater: hazards and policy responses. OECD studies on water. OECD Publishing, Paris2019Google Scholar and face a substantial challenge in mitigating rising local pollution levels emanating from patient excreta and inappropriate disposal,3Organisation for Economic Co-operation and DevelopmentPharmaceutical residues in freshwater: hazards and policy responses. OECD studies on water. OECD Publishing, Paris2019Google Scholar while simultaneously taking responsibility for the considerable manufacturing pollution externalities created through globalising their supply chains. Here, we present a UK case study that illustrates the scale of the problem and demonstrates the need for a cohesive, cross-sectoral systems approach. The UK is a HIC with a large pharmaceutical industry (£36·7 billion turnover in 2019),6Office for Life SciencesBioscience and health technology sector statistics 2019. Office for Life Sciences, London2020Google Scholar a well recognised health-care pharmaceutical market (the UK National Health Service [NHS]), and a diverse water industry comprising both private and public operators working on regional and national scales. Efforts to reduce pharmaceutical pollution derived from UK health care face numerous significant challenges: first, NHS pharmaceutical supply chains are complex and traverse institutional, sectoral, and national boundaries, so defining the environmental impacts of manufacture and supply, and assigning accountability for them, is difficult and disjointed;3Organisation for Economic Co-operation and DevelopmentPharmaceutical residues in freshwater: hazards and policy responses. OECD studies on water. OECD Publishing, Paris2019Google Scholar second, pharmaceutical usage is extensive and rising, with pharmaceuticals being the second biggest cost of the NHS (£16·8 billion annually);7National Health ServiceNHS website.https://www.england.nhs.uk/Date accessed: July 11, 2022Google Scholar third, UK regulations do not allow recycling of pharmaceuticals,4Alshemari A Breen L Quinn G Sivarajah U Can we create a Circular Pharmaceutical Supply Chain (CPSC) to reduce medicines waste?.Pharmacy. 2020; 8: 221Crossref Google Scholar with a substantial proportion of unused and expired drugs inappropriately disposed of into land or water waste;4Alshemari A Breen L Quinn G Sivarajah U Can we create a Circular Pharmaceutical Supply Chain (CPSC) to reduce medicines waste?.Pharmacy. 2020; 8: 221Crossref Google Scholar fourth, removal of pharmaceuticals from UK wastewater treatment plants is incomplete and highly variable,3Organisation for Economic Co-operation and DevelopmentPharmaceutical residues in freshwater: hazards and policy responses. OECD studies on water. OECD Publishing, Paris2019Google Scholar with treated effluent water and waste (sludge) containing pharmaceutical residues of concern often directly released to the environment; fifth, untreated waste containing health-care pharmaceuticals regularly enters the UK environment directly, through off-grid, septic-tank systems and combined sewer overflows; sixth, environmental levels of most pharmaceuticals are not regularly monitored, and of the 1912 pharmaceuticals registered in UK health care,5Burns EE Carter LJ Snape J Thomas-Oates J Boxall ABA Application of prioritization approaches to optimize environmental monitoring and testing of pharmaceuticals.J Toxicol Environ Health B Crit Rev. 2018; 21: 115-141Crossref PubMed Scopus (48) Google Scholar only eight are regularly monitored in UK waters (EU watch list 2022/1307); and finally, few pharmaceuticals used in UK health care have comprehensive data on environmental impacts, with only 11% having any substantive ecotoxicology data in the public domain.5Burns EE Carter LJ Snape J Thomas-Oates J Boxall ABA Application of prioritization approaches to optimize environmental monitoring and testing of pharmaceuticals.J Toxicol Environ Health B Crit Rev. 2018; 21: 115-141Crossref PubMed Scopus (48) Google Scholar Systems thinking is increasingly used to interpret and manage complex issues. We charted the flow of pharmaceutical stock used in UK health care, and the most important factors influencing this flow (figure). Our systems map illustrates the inherent interconnectivity between the health, pharmaceutical, and environmental sectors, and outlines pathways for the integration of policies and frameworks between these. For example, the recent Organisation for Economic Co-operation and Development report on the Management of Pharmaceutical Household Waste8Organisation for Economic Co-operation and DevelopmentManagement of pharmaceutical household waste: limiting environmental impacts of unused or expired medicine. OECD Publishing, Paris2022Google Scholar could be integrated into health-care system strategies, including NHS net-zero and over-prescribing policies.7National Health ServiceNHS website.https://www.england.nhs.uk/Date accessed: July 11, 2022Google Scholar Our map also identifies opportunities to improve cross-sectoral interconnectivity, for example it highlights the scarcity of feedback from the environmental sector into points controlling the flow of pharmaceutical stock through the system (licencing, reimbursement, procurement, and prescription), and the complete absence of feedback relating to international manufacturing pollution. This demonstrates the need for expansion of environmentally responsible initiatives to cover global supply chains, for example in ecopharmacovigilance schemes developed by UK pharmaceutical companies, and in NHS procurement policies. An abundance of potential interventions already exist across the UK health-care-derived pharmaceutical pollution system (appendix). Many of these interventions are aimed at reducing the rate or impact of pharmaceuticals flowing into the environment, for example through greener pharmaceutical design, improved disposal or increased removal from wastewater. From a broader systems perspective, the most effective way to reduce pharmaceutical outflow is likely to be through reducing inflow—ie, by addressing the upstream market forces driving unnecessary pharmaceutical usage. This strategy echoes calls from wider sustainable health-care strategies for greater prioritisation and investment into preventative health care and non-pharmaceutical treatment options. However, like many of the interventions identified (appendix), this is not straightforward, demonstrating the need to consider competing social, health, economic, and environmental factors when designing system-wide intervention strategies. As such, adoption of a systems approach will require dedicated cross-sectoral platforms, with resources and funding to engage and support the major stakeholder groups in jointly discussing, researching, prioritising, and adopting system-wide approaches. The One Health Breakthrough Partnership in Scotland is a successful model of such a multiagency systems approach. With pharmaceutical production predominantly (and increasingly) based in low-income and middle-income countries (LMICs),3Organisation for Economic Co-operation and DevelopmentPharmaceutical residues in freshwater: hazards and policy responses. OECD studies on water. OECD Publishing, Paris2019Google Scholar these populations face the greatest burden of manufacturing pollution despite an estimated 2 billion people still no having access to essential medicines and sanitation.9Chan M Ten years in public health. WHO, Geneva2017Google Scholar There is also a long tradition of sending unused medical products near their expiry date to LMICs, potentially leaving them with large stocks of out-of-date medicines without safe disposal options.10Bero L Medical donations are not always free: an assessment of compliance of medicine and medical device donations with World Health Organization guidelines (2009-2017).Int Health. 2019; 11: 379-402Crossref PubMed Scopus (17) Google Scholar Thus, HICs have an urgent responsibility to identify and implement strategies to mitigate their global pollution footprint. Initiatives such as the PREMIER project are supporting this, by addressing the scarcity and access to data on the environmental impacts of pharmaceutical pollution,3Organisation for Economic Co-operation and DevelopmentPharmaceutical residues in freshwater: hazards and policy responses. OECD studies on water. OECD Publishing, Paris2019Google Scholar to inform decision making. Mitigating global pharmaceutical pollution derived from health care is essential for achieving sustainable health-care systems, and for helping to restore humanity back within the safe operating space of the chemical pollution planetary boundary.1Persson L Carney Almroth BM Collins CD et al.Outside the safe operating space of the planetary boundary for novel entities.Environ Sci Technol. 2022; 56: 1510-1521Crossref PubMed Scopus (301) Google Scholar Future efforts must also be integrated with broader sustainable development issues, such as those targeting equitable access to health-care pharmaceuticals and veterinary pharmaceutical usage. These issues are inextricably linked to pharmaceutical pollution derived from health care and pose key barriers to a sustainable global pharmaceutical future. SO is a shareholder and employee of AstraZeneca. KT was supported by awards from the Transdisciplinary Research Initiatives Fund at the Environment and Sustainability Institute and the Wellcome Trust Translational Research Exchange at Exeter (TREE), both at the University of Exeter (Exeter, UK). Online workshops were organised with support from the Continuing Professional Development Team at the University of Exeter, funded by the National Institute of Health and Social Care School for Public Health (University of Exeter) and the Dr Edouard Delcroix Prize in Oceans and Human Health, awarded to Prof Lora Fleming. The infographic in the figure was commissioned to Dr Will Stahl-Timmins (blog.willstahl.com), and jointly funded by TREE and a Natural Environment Research Council-funded Knowledge Exchange Fellowship awarded to Prof Will Gaze (reference NE/V019279/1). Download .pdf (.42 MB) Help with pdf files Supplementary appendix